4.6 Article

Long-term maintenance of a microfluidic 3D human liver sinusoid

Journal

BIOTECHNOLOGY AND BIOENGINEERING
Volume 113, Issue 1, Pages 241-246

Publisher

WILEY-BLACKWELL
DOI: 10.1002/bit.25700

Keywords

liver-on-a-chip; microfludics; liver sinusoid; hepatocytes; 3D microtissue

Funding

  1. NCATS [UH2TR000503]
  2. NIDDK [F32DK098905, K99DK095984]
  3. NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UH3TR000503, UH2TR000503] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R21EB020192, P41EB002503] Funding Source: NIH RePORTER
  5. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K99DK095984, F32DK098905] Funding Source: NIH RePORTER

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The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip, using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic) and urea excretion (detoxification) were observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies. Biotechnol. Bioeng. 2016;113: 241-246. (c) 2015 Wiley Periodicals, Inc.

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